rs869320734

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM4PP3PP5_Moderate

The NM_032638.5(GATA2):​c.1084_1095del​(p.Arg362_Asn365del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R362R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

GATA2
NM_032638.5 inframe_deletion

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.95
Variant links:
Genes affected
GATA2 (HGNC:4171): (GATA binding protein 2) This gene encodes a member of the GATA family of zinc-finger transcription factors that are named for the consensus nucleotide sequence they bind in the promoter regions of target genes. The encoded protein plays an essential role in regulating transcription of genes involved in the development and proliferation of hematopoietic and endocrine cell lineages. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1
In a hotspot region, there are 9 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 10 uncertain in NM_032638.5
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_032638.5.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
Variant 3-128481866-CGTTGGCGTTTCG-C is Pathogenic according to our data. Variant chr3-128481866-CGTTGGCGTTTCG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 29713.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-128481866-CGTTGGCGTTTCG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GATA2NM_001145661.2 linkuse as main transcriptc.1084_1095del p.Arg362_Asn365del inframe_deletion 6/7 ENST00000487848.6
GATA2NM_032638.5 linkuse as main transcriptc.1084_1095del p.Arg362_Asn365del inframe_deletion 5/6 ENST00000341105.7
GATA2NM_001145662.1 linkuse as main transcriptc.1042_1053del p.Arg348_Asn351del inframe_deletion 5/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GATA2ENST00000341105.7 linkuse as main transcriptc.1084_1095del p.Arg362_Asn365del inframe_deletion 5/61 NM_032638.5 P1P23769-1
GATA2ENST00000487848.6 linkuse as main transcriptc.1084_1095del p.Arg362_Asn365del inframe_deletion 6/71 NM_001145661.2 P1P23769-1

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Monocytopenia with susceptibility to infections Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMSep 08, 2011- -
Deafness-lymphedema-leukemia syndrome;CN300066:GATA2 deficiency with susceptibility to MDS/AML Pathogenic:1
Likely pathogenic, criteria provided, single submittercurationMolecular Pathology Research Laboratory, SA PathologyJul 06, 2021PS4_Supporting, PM2, PM4_Strong -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs869320734; hg19: chr3-128200709; API